The Effect of Saturated Fat Ingestion on the HDL Proteome The candidate: Hussein Yassine completed his residency at Case Western Reserve University with additional research training in exercise physiology at Schwartz Center of Metabolism by Dr. John Kirwan. He then joined the endocrinology program at the University of Arizona and trained in proteomics research under the supervision of Dr. Serrine Lau. Dr. Yassine has a strong interest in translational research. He is currently an Assistant Professor at the University of Arizona. Career Goals: Dr. Yassine's career goal is to be an outstanding physician-scientist. The goal is achieved by advancing cardiovascular research, contributing to the scientific society and providing excellent patient care. Institution: The University of Arizona has a state-of-the-art proteomics consortium and laboratory. Dr. Serrine Lau is a world renowned toxicologist and the director of the Arizona Proteomics Consortium with a strong interest in biomarker discovery using state-of-the art proteomic technology. Mentoring Team and Faculty Roles: Dr. Serrine Lau is the applicant's primary mentor, and will be responsible for advancing the applicant's career during the award phase. Dr. Lau has trained a large number of currently active, independent and successful scientists. Drs. George Tsaprailis and Linda Breci (proteomics core) will provide training in proteomics through courses, and hands on workshops. Dr. Craig Stump, Chief of Endocrinology and an expert in oxidative stress, and Dr. Stanley Goldberg, an expert in lipid disorders, will provide mentorship in clinical research, and will ensure that Dr. Yassine will have the resources to develop into an independent physician-scientist. Dr. Dean Billheimer, an expert in biostatistics for biomarker discovery, is committed to developing Dr. Yassine's biostatistics background through formal meetings, workshops and seminars. The applicant will consult with Dr. Peter Reaven on clinical cohort design, inflammation and cardiovascular disease. An advisory team of successfully funded scientists (Drs. Price, Funk, Vercelli) is formed to assess research progress and transitioning into independence. Project description: HDL, or good cholesterol, is considered one of the most important blood measures in predicting death, heart attacks and strokes. The mechanism of how HDL protects against atherosclerosis and cardiovascular disease is poorly understood. HDL consists of a lipid core and a wide array of attached proteins involved in inflammation and blood clot formation. Saturated fat intake in the diet increases the risk of cardiovascular disease with modest increases in HDL cholesterol concentrations, but its effect on HDL attached proteins is not known. We hypothesize that subjects with diabetes and cardiovascular disease have HDL enriched with inflammatory and prothrombotic proteins, and that a saturated fatty diet generates an HDL particle enriched in inflammatory proteins. The University of Arizona possesses a world- renowned proteomics research facility that discovers proteins at very low concentrations. Our first aim is to employ proteomic technologies to identify HDL proteome phenotypes in subjects with and without diabetes and cardiovascular disease. Our second aim is to identify the changes of the HDL protein cargo after ingesting a cup of heavy whipped cream. This discovery could help us understand the composition changes of HDL involved in cardiovascular disease, and serve as a marker to develop novel therapies aimed at decreasing the cardiovascular disease burden.